The overall objective of the proposed research is to determine the mechanism underlying the age-related accumulation of the autofluorescent pigment lipofuscin in the retinal pigment epithelium (RPE) and whether lipofuscin plays a role in age-related retinal diseases. A central focus is to better understand how vitamin A participates in RPE lipofuscin generation, including the possibility that retinal modification of rod outer segment (ROS) proteins accounts for a significant fraction of RPE lipofuscin. Three specific aims are proposed: (1) determine the molecular composition of human RPE lipofuscin; (2) determine whether RPE lipofuscin constituents turn over; and (3) determine whether light exposure to the retina promotes lipofuscin accumulation in the RPE.